Lipid metabolism and lipid signals in aging and longevity

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(10), P. 1394 - 1407

Published: April 22, 2021

Language: Английский

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In Vivo Three‐Photon Imaging of Lipids using Ultrabright Fluorogens with Aggregation‐Induced Emission

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(11)

Published: Feb. 11, 2021

Abstract Fluorescent probes capable of in vivo lipids labeling are highly desirable for studying lipid‐accumulation‐related metabolic diseases, such as nonalcoholic fatty liver disease, type‐2 diabetes, and atherosclerosis. However, most the current lipid‐specific fluorophores cannot be used due to their strong hydrophobicity. Herein, organic dots from bright luminogens with aggregation‐induced emission (AIEgen) developed three‐photon fluorescence imaging lipid‐rich tissues, liver, atherosclerotic plaques brain vasculatures, carotid arteries. The show excellent stability an aqueous medium high targeting specificity far‐red/near‐infrared (NIR) region under NIR‐II laser excitation, which enables efficient deep tissues. study will inspire development lipid‐targeting applications.

Language: Английский

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Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 16, 2021

Abstract Mitochondria play a pivotal role in the generation of signals coupling metabolism with neurotransmitter release, but for mitochondrial-produced ROS regulating neurosecretion has not been described. Here we show that endogenously produced hydrogen peroxide originating from axonal mitochondria (mtH 2 O ) functions as signaling cue to selectively regulate secretion FMRFamide-related neuropeptide (FLP-1) pair interneurons (AIY) C. elegans . We pharmacological or genetic manipulations increase mtH levels lead increased FLP-1 is dependent upon dismutation, mitochondrial calcium influx, and cysteine sulfenylation calcium-independent PKC family member PKC-1. -induced activates oxidative stress response transcription factor SKN-1/Nrf2 distal tissues protects animals ROS-mediated toxicity. AIY neurons, SKN-1 activity are rapidly reversibly regulated by exposing different bacterial food sources. These results reveal previously unreported linking diet-induced changes homeostasis secretion.

Language: Английский

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Lysosome lipid signalling from the periphery to neurons regulates longevity

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(6), P. 906 - 916

Published: June 1, 2022

Abstract Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism implicated ageing-associated metabolic neurodegenerative diseases. However, how actively coordinates the nervous systems to regulate ageing remains unclear. Here we report a fat-to-neuron lipid signalling pathway induced by its longevity-promoting role Caenorhabditis elegans . We discovered lipolysis peripheral fat storage tissue upregulates neuropeptide system promote longevity. This cell-non-autonomous regulation is mediated specific polyunsaturated fatty acid, dihomo-γ-linolenic LBP-3 chaperone protein transported from neurons. binds acts through NHR-49 nuclear receptor NLP-11 neurons extend lifespan. These results reveal lysosomes as hub coordinate ageing, inter-tissue communication promoting

Language: Английский

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Application of Caenorhabditis elegans in Lipid Metabolism Research

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1173 - 1173

Published: Jan. 7, 2023

Over the last decade, development and prevalence of obesity have posed a serious public health risk, which has prompted studies on regulation adiposity. With ease genetic manipulation, diversity methods for characterizing body fat levels, observability feeding behavior, Caenorhabditis elegans (C. elegans) is considered an excellent model exploring energy homeostasis cellular storage. In addition, homology with mammals in genes related to lipid metabolism allows many aspects modulation by regulators central nervous system be conserved this ideal organism. recent years, as complex network that maintain balance been gradually expanded refined, regulatory mechanisms storage become clearer. Furthermore, devices assess levels powerful tool droplet biology nematode metabolism. Herein, based rapid progress C. metabolism-related studies, review outlined metabolic processes, major signaling pathways regulation, primary experimental content nematodes. Therefore, holds great promise facilitating understanding, management, therapies human other diseases.

Language: Английский

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Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 19, 2024

Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic signaling functions. Both lysosomal have been linked longevity regulation; however, how lysosomes adjust their protein composition accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated four different mechanisms. We discovered recruitment AMP-activated kinase nucleoporin requirements for in response increased lipolysis. Through comparative analyses from tissues labeled markers, further elucidated heterogeneity across as well enrichment Ragulator complex on Cystinosin-positive lysosomes. Together, work uncovers proteome multiple scales provides resources understanding contribution dynamics transduction, organelle crosstalk, organism longevity.

Language: Английский

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Quantitative Structure–Activity Relationship Enables the Rational Design of Lipid Droplet-Targeting Carbon Dots for Visualizing Bisphenol A-Induced Nonalcoholic Fatty Liver Disease-like Changes

ACS Applied Materials & Interfaces, Journal Year: 2021, Volume and Issue: 13(37), P. 44086 - 44095

Published: Sept. 13, 2021

Lipid droplets (LDs) play indispensable roles in numerous physiological processes; hence, the visualization of dynamic behavior LDs living cells is great importance and pathological research. In this article, quantitative structure-activity relationship (QSAR) theory was employed as an effective design strategy for development organelle-targeting carbon dots (CDs). The lipid-water partition coefficient (Log P) QSAR adopted a key parameter to predict cellular uptake subcellular localization CDs live cells. By carefully adjusting molecular structure lipophilicity precursors, p-phenylenediamine-derivatized nucleolus-targeting hydrophilic were converted lipophilic [4-piperidinoaniline (PA) CDs] with inherent LD-targeting performance. PA able indicate visualize changes bisphenol A-induced nonalcoholic fatty liver disease-like model. demonstrated here expected be increasingly exploited powerful tool developing various CDs.

Language: Английский

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Host and microbiota metabolic signals in aging and longevity

Nature Chemical Biology, Journal Year: 2021, Volume and Issue: 17(10), P. 1027 - 1036

Published: Sept. 22, 2021

Language: Английский

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SRS-FISH: A high-throughput platform linking microbiome metabolism to identity at the single-cell level

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(26)

Published: June 21, 2022

One of the biggest challenges in microbiome research environmental and medical samples is to better understand functional properties microbial community members at a single-cell level. Single-cell isotope probing has become key tool for this purpose, but current detection methods determination incorporation into single cells do not allow high-throughput analyses. Here, we report on development an imaging-based approach termed stimulated Raman scattering-two-photon fluorescence situ hybridization (SRS-FISH) metabolism identity analyses communities with resolution. SRS-FISH offers imaging speed 10 100 ms per cell, which two three orders magnitude faster than achievable by state-of-the-art methods. Using technique, delineated metabolic responses 30,000 individual various mucosal sugars human gut via deuterium from heavy water as activity marker. Application investigate utilization host-derived nutrients major taxa revealed that response tends be dominated Bacteroidales, unexpected finding Clostridia can outperform Bacteroidales foraging fucose. With high sensitivity speed, will enable researchers probe fine-scale temporal, spatial, patterns complex unprecedented detail.

Language: Английский

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Stimulated Raman Scattering Imaging Sheds New Light on Lipid Droplet Biology

The Journal of Physical Chemistry B, Journal Year: 2023, Volume and Issue: 127(11), P. 2381 - 2394

Published: March 10, 2023

A lipid droplet (LD) is a dynamic organelle closely associated with cellular functions and energy homeostasis. Dysregulated LD biology underlies an increasing number of human diseases, including metabolic disease, cancer, neurodegenerative disorder. Commonly used staining analytical tools have difficulty providing the information regarding distribution composition at same time. To address this problem, stimulated Raman scattering (SRS) microscopy uses intrinsic chemical contrast biomolecules to achieve both direct visualization dynamics quantitative analysis high molecular selectivity subcellular level. Recent developments tags further enhanced sensitivity specificity SRS imaging without perturbing activity. With these advantages, has offered great promise for deciphering metabolism in single live cells. This article overviews discusses latest applications as emerging platform dissect health disease.

Language: Английский

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